D and Co Q-10 both show promise in treating Congestive Heart Failure
D research has taken a turn. For the last half dozen years research on
vitamin D has focused on linking deficiency with development of morbidity.
Links between low vitamin D status and a variety of disease have been
demonstrated ranging from auto immune diseases such as rheumatoid arthritis,
diabetes and multiple sclerosis to cancer.
focus of research is shifting. Now researchers have begun to ask whether
vitamin D supplementation can change the course of these diseases.
paper appeared in this month's edition of the American Journal of Clinical
Nutrition reporting on the effect of vitamin D on patients with Congestive
Heart Failure (CHF).
researchers gave 2,000 IU/day of vitamin D in a randomized, placebo-controlled
study involving 123 subjects with congestive heart failure (CHF). Subjects
were divided into two groups. Group 1 received vitamin D and calcium (500
mg/day), while Group 2 (control group) received a placebo and calcium.
93 patients completed the study. Group 1, the vitamin D people, had a
43% increase in interleukin-10 (IL-10), an anti-inflammatory cytokine,
and a significant decrease in parathyroid hormone. Subjects in Group 2,
the placebo group, had a 12% increase in, tumor necrosis factor-alpha
(TNF-alpha), a pro-inflammatory cytokine, while the vitamin D group did
not. These pro-inflammatory cytokines may contribute to development of
CHF. There was no statistically significant difference in survival dat
15 months. Even so the fact that vitamin D could reduce inflammation in
patients with CHF lead the authors to suggest CHF patients could benefit
from 2,000 IU of vitamin D per day. [i]
in 1997 an article in the American Journal of Medicine reported that people
with CHF had surprisingly low vitamin D levels. About half of people with
severe CHF had osteopenia or osteoporosis. Markers of bone turnover were
frequently abnormal and were more so with more severe disease. [ii]
A report a few years later linked low vitamin D and resulting high
parathyroid hormones with CHF. [iii]
These studies are not surprising as the epidemiological link between
sun exposure on heart disease risk is well established.
is new is the attempt to measure benefit in treating CHF with vitamin
D supplementation. Just because deficiency causes or is associated with
a disease, it does not necessarily follow that supplementations will cure
the disease. Although we wouldn't complain even if it just helped treat
it. Expect to see results of other intervention trials with Vitamin D
being supplemented in diseases which have been linked to deficiency.
on the subject of congestive heart failure another interesting study showed
up last November in the European Heart Journal, this one using a multivitamin
plus Coenzyme Q-10 at 150 mg/day. The multivitamin/mineral supplement
contained high levels of vitamins B 1 and B 6 (200 mg each), folic acid
(5000 mcg), B 12 (200 mcg), vitamin C (500 mg), vitamin E (400 IU). In
the placebo group the disease continued to progress: left ventricular
volumes increased 4% in the placebo group but decreased 13% in the supplemented
group. Left ventricular ejection fraction remained essentially unchanged
in the placebo group while improving 21% in the supplemented group. Quality-of-life
scores improved 9.5% in the supplemented group while declining 1% in the
placebo group. [iv]
results are interesting if just a little confusing to practitioners. Earlier
trials have shown that CoQ10 improves heart function in CHF patients.
Unfortunately, in the current study there is no way to separate the effect
of the Co Q-10 from that of the vitamins. We don't know whether the effect
came from the Co Q-10 alone or the multivitamins increased the benefit
further. For the time being adding multivitamins in addition to Co Q-10
should be done on the basis of the, “can't hurt and might help” principle.
Vitamin D supplementation improves cytokine profiles
in patients with congestive heart failure: a double-blind, randomized,
SS , Zittermann
A , Tenderich
G , Berthold
HK , Stehle
P , Koerfer
Institute of Nutrition and Food Science, University of Bonn , Bonn , Germany
BACKGROUND: Elevated circulating concentrations of proinflammatory cytokines
may contribute to the pathogenesis of congestive heart failure (CHF).
In vitro studies suggest that vitamin D suppresses proinflammatory cytokines
and increases antiinflammatory cytokines. OBJECTIVE: We evaluated the
effect of vitamin D supplementation on the survival rate and different
biochemical variables in patients with CHF. DESIGN: One hundred twenty-three
patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d
[D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical
variables were assessed at baseline and after 9 mo. The survival rate
was calculated for a follow-up period of 15 mo. RESULTS: Ninety-three
patients completed the study. Significant treatment effects were observed
on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D
(P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha
(P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased
by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the
D(-) group. Compared with baseline, parathyroid hormone was significantly
lower and the antiinflammatory cytokine interleukin 10 was significantly
higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor
necrosis factor alpha increased in the D(-) group but remained constant
in the D(+) group. The survival rate did not differ significantly between
the study groups during the follow-up period. CONCLUSIONS: Vitamin D(3)
reduces the inflammatory milieu in CHF patients and might serve as a new
antiinflammatory agent for the future treatment of the disease. Our data
provide evidence for the involvement of an impaired vitamin D-parathyroid
hormone axis in the progression of CHF.
PMID: 16600924 [PubMed - in process]
J Med. 1998 May;104(5):508-9.
J Med. 1998 Oct;105(4):358.
J Med. 1998 Oct;105(4):358-9.
J Med. 1999 Jul;107(1):102-3.
Bone mass, vitamin D deficiency, and hyperparathyroidism
in congestive heart failure.
E , Mancini
D , Aaronson
K , Silverberg
SJ , Seibel
MJ , Addesso
V , McMahon
Department of Medicine, College of Physicians and Surgeons, Columbia University,
New York , New York 10032 , USA .
PURPOSE: In contrast to renal and hepatic failure, congestive heart failure
(CHF) has not been associated with a defined metabolic bone disorder.
However, low bone mass has been reported in patients with CHF who receive
a cardiac transplant. Both the pathophysiology and therapy of CHF may
influence bone and mineral homeostasis and evidence that calciotropic
hormones may affect cardiovascular function is accumulating. Therefore,
we evaluated patients with severe CHF to determine the prevalence of osteoporosis
and to characterize relationships between mineral homeostasis, bone turnover,
bone mass, and severity of CHF. PATIENTS AND METHODS: One hundred one
patients (79 men and 22 women, aged 25 to 70 years) with severe CHF (New
York Heart Association functional class III or IV) referred for consideration
for cardiac transplantation were evaluated with measurements of serum
25-hydroxyvitamin D (25-OHD), 1,25 dihydroxyvitamin D [1,25(OH)2D], intact
parathyroid hormone (PTH), markers of bone turnover (serum osteocalcin,
urinary hydroxyproline, and pyridinium crosslinks); bone mineral density
(BMD) by dual energy x-ray absorptiometry was measured in 91 patients.
Left ventricular ejection fraction (LVEF) and resting cardiac output (CO)
were determined in 88 and maximal treadmill exercise testing and peak
oxygen consumption were performed in 45 patients. RESULTS: Osteoporosis
(T score < or = -2.5) was present in 7% at the lumbar spine, 6% at
the total hip, and 19% at the femoral neck. Osteopenia (T scores between
-1.0 and -2.5) was present in 43% at the lumbar spine, 47% at the total
hip, and 42% at the femoral neck. Women were more severely affected (P
= 0.007). Frankly low serum 25-OHD (< or = 9 pg/mL) and 1,25(OH)2D
(< or = 15 pg/mL) levels were found in 17% and 26% of the patients,
respectively, and elevated serum PTH (> or = 65 pg/mL) in 30%. Both
low serum 1,25(OH)2D and increased serum PTH were associated with prerenal
azotemia. Low serum vitamin D metabolites were associated with biochemical
evidence of increased bone turnover, but BMD did not differ by vitamin
D or PTH status. Patients with more severe CHF had significantly lower
vitamin D metabolites and higher bone turnover, whereas elevated PTH was
associated with better LVEF (21 +/- 1 versus 18 +/- 1%; P = 0.05) and
correlated positively with resting CO (R = 0.220; P = 0.04). CONCLUSIONS:
Osteopenia or osteoporosis were observed in approximately half of these
patients with severe CHF. Abnormal calciotropic hormone concentrations,
also common, were associated with evidence of increased bone resorption
but were not related to BMD in this cross-sectional study. Abnormal concentrations
of calciotropic hormones were related to the severity of cardiovascular
compromise. Because both low BMD and low serum concentrations of 25-OHD
in patients with CHF are associated with higher rates of bone loss and
fracture after cardiac transplantation, patients should be evaluated for
and receive appropriate therapy for these disorders.
PMID: 9316552 [PubMed - indexed for MEDLINE]
Low vitamin D status: a contributing factor in
the pathogenesis of congestive heart failure?
A , Schleithoff
SS , Tenderich
G , Berthold
HK , Korfer
R , Stehle
Department of Nutrition Science, University of Bonn , Germany . firstname.lastname@example.org
OBJECTIVES: This study was designed to evaluate the association between
vitamin D status and congestive heart failure (CHF). BACKGROUND: Impaired
intracellular calcium metabolism is an important factor in the pathogenesis
of CHF. The etiology of CHF, however, is not well understood. METHODS:
Twenty patients age <50 years and 34 patients age >/=50 years with
New York Heart Association classes >/=2 and 34 control subjects age
>/=50 years were recruited. N-terminal pro-atrial natriuretic peptide
(NT-proANP), a predictor of CHF severity; vitamin D metabolites; and parameters
of calcium metabolism were measured in fasting blood samples collected
between November 2000 and March 2001. RESULTS: Both groups of CHF patients
had markedly increased serum levels of NT-proANP (p < 0.001), increased
serum phosphorus levels (p < 0.001), and reduced circulating levels
of both 25-hydroxyvitamin D (p < 0.001) and calcitriol (p < 0.001).
Albumin-corrected calcium levels were reduced and parathyroid hormone
levels were increased in the younger CHF patients compared with the controls
(both p values <0.001). Moreover, parathyroid hormone levels tended
to be higher in the elderly CHF patients than in the controls (p = 0.074).
In a nonlinear regression analysis 25-hydroxyvitamin D and calcitriol
were inversely correlated with NT-proANP (r(2) = 0.16; p < 0.001 and
r(2) = 0.12; p < 0.01, respectively). The vitamin D genotype at the
BmsI restriction site did not differ between the study groups. CONCLUSIONS:
The low vitamin D status can explain alterations in mineral metabolism
as well as myocardial dysfunction in the CHF patients, and it may therefore
be a contributing factor in the pathogenesis of CHF.
PMID: 12570952 [PubMed - indexed for MEDLINE]
The effect of micronutrient supplementation on
quality-of-life and left ventricular function in elderly patients with
chronic heart failure.
KK , Nikitin
NP , Parker
AC , von
Haehling S , Volk
HD , Anker
SD , Clark
AL , Cleland
Department of Academic Cardiology, Castle Hill Hospital , Castle Road
, Cottingham, Hull HU16 5JQ , UK . email@example.com
AIMS: Chronic heart failure (CHF) is a common and leading cause of death
in industrialized countries. The potential benefits of micronutrient supplementation
in CHF are extensive. Therefore, we examined the influence of long-term
multiple micronutrient supplementation on left ventricular ( LV ) function,
levels of pro-inflammatory cytokines, and quality-of-life (QoL) in elderly
patients with CHF. METHODS AND RESULTS: Thirty CHF patients [age 75.4
(0.7), mean (SEM), LV ejection fraction (LVEF) < or =35%] were randomized
to receive capsules containing a combination of high-dose micronutrients
(calcium, magnesium, zinc, copper, selenium, vitamin A, thiamine, riboflavin,
vitamin B(6), folate, vitamin B(12), vitamin C, vitamin E, vitamin D,
and Coenzyme Q10) or placebo for 9 months in a double-blind fashion. All
subjects were on stable optimal medical therapy for at least 3 months
before enrolment. At randomization and at study end, tumour necrosis factor-alpha
and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute
walk test and QoL were assessed. Cardiac magnetic resonance scanning was
performed to evaluate cardiac dimensions and LVEF. Two patients died during
follow-up. The remaining patients (14 randomized to placebo and 14 to
micronutrients) were well matched for LV function, symptoms, and exercise
capacity. At the end of the follow-up period, LV volumes were reduced
in the intervention group with no change in the placebo group [-13.1 (17.1)%
vs. +3.8 (10.0)%; P<0.05]. LVEF increased by 5.3+/-1.4% in the intervention
group and was unchanged in the placebo group (P<0.05). Patients taking
micronutrients also had a significant improvement in QoL score between
enrolment and study end [+9.5 (1.6)%; P<0.05], whereas those taking
placebo had a slight deterioration [-1.1 (0.8)%; P=0.12]. Six-minute walk
test and inflammatory cytokine levels remained unchanged in both groups.
CONCLUSION: Long-term multiple micronutrient supplementation can improve
LV volumes and LVEF and QoL scores in elderly patients with heart failure
due to LV systolic dysfunction.
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